FDA ALERT [3/21/2008]: FDA is highlighting the addition of information about hepatotoxicity to the WARNINGS section of the Prezista prescribing information.

FDA and Tibotec Therapeutics have reviewed information from clinical trials in which Prezista was administered and from postmarketing adverse event reports of hepatotoxicity in patients taking Prezista. While causality is not firmly established, an association between Prezista and hepatotoxicity is suspected.

Prezista, a protease inhibitor indicated for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment-experienced adult patients, is co-administered with ritonavir, an antiretroviral drug associated with hepatotoxicity. In general, HIV antiretroviral medications are associated with liver enzyme elevations, however, for some medications, an association with hepatotoxicity is more firmly established.

This information reflects FDA’s current analysis of data available to FDA concerning this drug. FDA intends to update this sheet when additional information or analyses become available.

To report any unexpected adverse or serious events associated with the use of this drug, please contact the FDA MedWatch program using the contact information at the bottom of this page.

The Prezista prescribing information includes new information in the WARNINGS section about the potential for hepatotoxicity, including acute hepatitis and cytolytic hepatitis, in patients taking Prezista.

Follow HIV treatment guidelines 1 for appropriate liver monitoring in all patients receiving Prezista. Patients with co-morbid conditions such as chronic active hepatitis B or C or patients with pre-treatment elevations of hepatic enzymes should be monitored more frequently.

Consider interrupting or discontinuing Prezista if evidence of new or worsening liver injury develops, including clinically significant elevation of liver enzymes and/or symptoms of hepatotoxicity.

Information for the patient:Physicians who prescribe Prezista should discuss with their patients:

Prezista, one drug in the class of protease inhibitors, in combination with ritonavir, is effective in treating HIV in some patients.

As with all medicines, side effects are possible. Liver damage is a potential serious side effect. Periodic blood tests will be necessary to monitor how your liver is working.

If you experience unexplained fatigue, loss of appetite, abdominal pain, nausea, yellowing of the skin, or dark urine, immediately contact your doctor. Your doctor will decide if you can continue taking Prezista, if Prezista needs to be temporarily discontinued, or if the treatment for your HIV infection should be changed.

Background Information and DataFDA has reviewed postmarketing reports of events related to the liver in association with Prezistause. The contribution of Prezista to the events related to the liver (hepatic failure, hepatic necrosis, cirrhosis, hepatitis, jaundice and increased liver function tests) is considered possible in 24 cases. All subjects were taking other medications or had underlying medical conditions that may have contributed to liver injury. Nine of the 24 cases reported co-infection with hepatitis B or C, while 15 cases did not report co-infection with hepatitis B or C.

Among the most convincing cases from clinical trials and postmarketing reports that had a potential relationship to Prezista were the following:

A biopsy proven case of drug-induced liver injury in a patient with a history of alcohol use.

A case of acute hepatitis with increased liver enzymes in a patient co-infected with chronic hepatitis B. The acute hepatitis with increased liver enzymes abated after Prezista and other antiretrovirals were discontinued and recurred after Prezista and other antiretrovirals were restarted.

Two cases of biopsy proven drug-induced liver injury in patients not reported to be co-infected with hepatitis B or C.

A case of acute hepatitis with a drug-induced hypersensitivity reaction in a patient with chronic hepatitis B. All antiretrovirals were temporarily discontinued and restarted except Prezista. The acute hepatitis did not recur.

FDA has worked with the maker of Prezista, Tibotec Therapeutics, to include information about hepatotoxicity in the Warnings section of the Prezista prescribing information.